PRODUCT profiles

Jim Middleton, BS, RPh

Published Online: Thursday, November 1, 2007

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Carvedilol Regular-release Tablets

Alpha- and beta-blocking drugs are
used in the treatment of hypertension,
and when 1 drug can combine the receptor
blockade, it should be expected to
enhance therapeutic outcomes. Carvedilol,
a nonselective beta-blocker with
selective alpha-1 blocking actions,
appears to offer better results than
agents possessing only 1 variety of
receptor-blocking activity. Carvedilol is
available in 3.125-, 6.25-, 12.5-, and 25-
mg tablet strengths from Apotex Inc,
Caraco Pharmaceutical Laboratories, and
Mylan Laboratories.

The beneficial actions for beta-blockers
in congestive heart failure are based
on theoretical action, suggesting a
decrease of sympathetic outflow at the
cardiac level or an alteration in renin
release. The additional effect of alpha-1
blockade with carvedilol results in general
peripheral arterial and venous dilation,
with the effects on standing blood pressure
being the most pronounced.

In general, beta-blockers are indicated
for the treatment of hypertension,
angina, and heart failure.
Although carvedilol can be used as
monotherapy, it is usually employed in
conjunction with other drug management
options (digoxin, thiazides, angiotensin-
converting enzyme [ACE] inhibitors)
to increase patient survival and
reduce the frequency of hospitalization.

The nonselectivity of the beta-blocking
effect of carvedilol means that bronchial
asthma is a specific contraindication to
its use, with deaths reported following
even a single dose. It also is not recommended
in the presence of hepatic
impairment or among the elderly.

Dosing for hypertension starts at 6.25
mg twice daily, with an upper limit of 25
mg twice daily. For congestive heart failure,
the dose is 3.125 mg twice daily,
gradually titrating to response or to a
maximum of 6.25 mg twice daily. Oral
dosing is little affected by food. In polytherapy,
however, carvedilol should be
administered 2 hours prior to an ACE
inhibitor to reduce orthostatic hypotension
and other symptoms of general vasodilation.
In addition, cessation of therapy
should be done gradually to prevent
rebound pressor effects.

Among patients hospitalized with congestive
heart failure or left ventricular cardiac
dysfunction, discharge
use of drugs with
beta-blocking effects has
shown a significant reduction
in mortality.

Verapamil Extended-release Capsules (PM)

Extended-release verapamil
(PM) is available in capsule form in
100-, 200-, and 300-mg strengths from
Mylan Laboratories. Indications for verapamil
include the management of
Prinzmetal-variant, unstable, or chronic
stable angina; hypertension; and to control
ventricular rates at rest or with concurrent
atrial fibrillation. It also is used to
prevent the recurrence of paroxysmal
supraventricular tachycardia.

The effect of calcium channel blockers
such as verapamil on cardiac conduction
can create serious adverse effects, and
while the frequency is under 2% overall,
they can range from asymptomatic firstdegree
atrioventricular block to serious
third-degree block. Other adverse effects
from oral administration are seen in over
6% of users, requiring a reduction in
dose. The severity of the side effects increases
with concurrent use of betablockers
or digoxin. In some cases, the
negative inotropic effects associated
with verapamil can actually cause congestive
heart failure or pulmonary edema.
The most common complaint from
patients regarding verapamil is constipation.

To treat hypertension with the extended-
release capsule version of verapamil
(PM), the usual adult dose is 200 mg at
bedtime, with upward titration to a maximum
of 400 mg at bedtime. Blood pressure
measurements should be carefully
monitored.

Verapamil requires a reduced dose
among the elderly and should be used
cautiously with hepatic or renal impairment.
Verapamil also may both prolong
the effect of alcohol and increase blood
concentrations by up to 17%. Although
verapamil should be taken with food,
grapefruit poses a potential interaction
and should be avoided during this therapy.